ABSTRACT
OBJECTIVES: Observational studies indicate that insomnia may increase risk of peptic ulcer disease (PUD). Our purpose is to clarify the possible causal relationship between insomnia and PUD by Mendelian randomization analyses. METHODS: We carried out analyses using summary statistics data for genetic variants reported from a GWAS of insomnia (N = up to 1,331,010 individuals) and from a GWAS of PUD (N = up to 456,327 individuals). Three Mendelian randomization approaches were used to explore whether insomnia might play a causal role in PUD, and pathway and functional enrichment analyses were conducted to anticipate the underlying mechanisms. RESULTS: Conventional Mendelian randomization analysis showed clear causality between insomnia and PUD; 1 SD increased insomnia incident was related to a 19% higher risk of PUD (P = 6.69 × 10-16; OR, 1.19 (95% CI, 1.14-1.24)). The associations between insomnia and PUD were consistent in the other two analyses performed using the weighted median method (P = 7.75 × 10-7; OR, 1.16 (95% CI, 1.09-1.23)) and MR-Egger regression (P = 5.00 × 10-3; OR, 1.27 (95% CI, 1.07-1.50)). Moreover, no evidence indicated a reverse causality between PUD events and insomnia symptoms. Pathway and functional enrichment analyses indicated that the mechanisms of insomnia effect on PUD may be through various ways, such as the immune system and oxidative stress. CONCLUSIONS: This Mendelian randomization study suggests insomnia as a causal risk factor for PUD. The potential mechanisms included may be immune and oxidative stress. These findings indicate that improving sleep quality could have substantial health benefits.
Subject(s)
Mendelian Randomization Analysis/methods , Peptic Ulcer/epidemiology , Peptic Ulcer/genetics , Polymorphism, Single Nucleotide , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/genetics , Causality , Chromosome Mapping/methods , Databases, Genetic , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Humans , Incidence , Multigene Family , Risk Factors , Sleep QualityABSTRACT
Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457C-rs2069744T-rs20541A) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (padj = 0.019 and padj = 0.042, respectively). In subgroup population analyses, the variant rs1881457C was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (padj = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457C also significantly contributed to a nearly twofold risk of late-onset CAD (padj = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.
Subject(s)
Asian People/genetics , Coronary Artery Disease/etiology , Genetic Association Studies , Genetic Predisposition to Disease , Interleukin-13/genetics , Adult , Alleles , Case-Control Studies , China/epidemiology , Comorbidity , Coronary Artery Disease/epidemiology , Coronary Artery Disease/metabolism , Female , Humans , Interleukin-13/metabolism , Linkage Disequilibrium , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Risk AssessmentABSTRACT
This study was aimed at evaluating the influence of ethanol addition on diesel exhaust emissions and the toxicity of particulate extracts. The experiments were conducted on a heavy-duty diesel engine and five fuels were used, namely: E0 (base diesel fuel), E5 (5%), E10 (10%), E15 (15%) and E20 (20%), respectively. The regulated emissions (THC, CO, NOx, PM) and polycyclic aromatic hydrocarbon (PAH) emissions were measured, and Ames test and Comet assay, respectively, were used to investigate the mutagenicity and genotoxicity of particulate extracts. From the point of exhaust emissions, the introduction of ethanol to diesel fuel could result in higher brake specific THC (BSTHC) and CO (BSCO) emissions and lower smoke emissions, while the effects on the brake specific NOx (BSNOx) and particulate matters (BSPM) were not obvious. The PAH emissions showed an increasing trend with a growth of ethanol content in the ethanol-diesel blends. As to the biotoxicity, E20 always had the highest brake specific revertants (BSR) in both TA98 and TA100 with or without metabolizing enzymes (S9), while the lowest BSR were found in E5 except that of TA98-S9. DNA damage data showed a lower genotoxic potency of E10 and E15 as a whole.
